HERBAL MIX FOR TREATING UPPER RESPIRATORY DISEASES AND PHARMACEUTICAL FORMS BASED THEREON

The invention relates to medicine, more particularly to pharmaceutical production and can be used for elaborating therapeutic agent on the basis of herbal mix for treatment of (specific, and nonspecific) chronic and acute diseases of respiratory tracts (such as bronchitis (obstructive and nonobstructive), pneumonia, pleurisy, tuberculosis).

Respiratory tract diseases are the topical question of the modern therapy for their widespread nature and often for its severe proceeding and complication. Also, it is known that the disease such as lung tuberculosis, is treated with first-generation (streptomycin, Rifampicin, Isoniazid, Ethambutol) and second-generation (Kanamicin, Floromicin, Ethionamide, Cycloserine) preparations as well. At present these preparations are practically ineffective against the resistant form of lung tuberculosis, because they do not ensure not only the complete treatment of the disease, but also the halting the pathological process caused by the disease. Besides, the mentioned medications have many side effects and contraindications. Moreover, they are relatively expensive. Besides, many patients with pathologic of respiratory tract diseases undergo self-treatment at home under domestic conditions without doctor's supervision, which is why it is necessary that the therapeutic agent should consist of safe and effective, anti- inflammatory and anti-cough medicine, of which action will be directed to the reduction and elimination of main manifestations of the disease, despite whatever its etymology is.

Recently, the herbal preparations draw a great attention. Phyto preparations are better tolerated by humans, have rare side effects and complications. (Sokolov S. YA. Zamotaev I. P. " Directory of Medicinal Plants". M. 1984, P. 3, 4, 13).

It is known antiseptic and expectorant drugs: " Breast mix No 1", " Breast Collection No 2", " Breast mix N 3", "Althea Syrup" "Fitovit" etc.

" Breast mix N l" comprises Althea roots and Tussilago farfara, " Breast mix No 2" comprises licorice roots, Plantain leaves and Tussilago farfara, " Breast mix No 3" comprises Althea roots, licorice roots, Salvia leaves, anisic fruitage and Pinus sylvestris. Breast mixes NOl, N02, and NO 3 are not characterized by wide spectrum of pharmacological activity, that makes the organization of large-scale production of safe and effective medicines more difficult. (Mashkovski M.D. Medicinal Agents, part 1. M. "Medicine" 1984. p.359).

"Althea Syrup" contains Althea roots, sucrose and artificial aromatizers (Mashkovski M.D. Medicinal Agents, part 1. M. "Medicine" 1984. p.359). The composition of these therapeutic agents, on the one hand, makes impossible for diabetic patients to use these medicines, and on the second hand, increases the frequency of the allergic reactions.

"Fitovit" comprises swampy wild rosemary, knotweed herb, tall elecampane roots, narrow-leaved willow-herb leaves, small-leaved linden flowers, common coltsfoot leaves, medicinal lungwort herb, glabrous licorice roots, common pine buds, common thyme herb, tripartite bur-marigold herb, major celandine herb, medical marsh-mallow roots, birch buds, black elder flowers, medical valerian rhizomes, medicinal pot-marigold flowers, white mistletoe leaves, swampy cudweed herb, violet pansy flowers. (Patent of Russian Federation No 2185184, IPCI A61K35/78, 2002, "Bronchopulmonary species "Fitovit"). From the components of "Fitovit", major celandine herb, white mistletoe leaves and black elder flowers belong to the toxic plants class. Major celandine herb contains toxic isoquinoline class alkaloids: protopine, koptizine, berberine, sangvinarine, white mistletoe leaves contain glycoside - vyskotoxin, and black elder flowers - cyanogenic glycoside sambucus, which is converted into toxic material cyanhydric acid in body in the body (Manfrid Palov. Encyclopedia of Medicinal Plants. M.1988, p.80). The mentioned fact limits the future trends of "Fitovit" usage among children and aged individuals as well and requires strict dosage. Besides, the part of plants used in "Fitovit" (elecampane, common coltsfoot, white mistletoe leaves) have not been entered into the state pharmacopeia list, that makes the formation of the technological normative document of these plants and preparations too difficult and requires the long-term researches (phytochemical and preclinical) to be conducted for medicine registration.

The content of the mentioned mix is complex and extensive, that makes its manufacture difficult. Also the mentioned preparation does not give the opportunity to use it in wide therapy spectrum (e.g. treaty of tuberculosis).

The technical effect of this invention is broadening the assortment of therapeutic agent made of plant raw materials and creation of effective medicaments with a high therapeutic spectrum and, which usage shouldn't cause the side effects. The essence of the invention is herbal mix containing Althea officinalis, Inula helenium, Tussilago farfara, Pinus sylvestris, Salvia officinalis, Matricaria chamomilla L, Mentha piperita, leonurus quinquelobatus, Calendula officinalis and Thymus vulgaris L or Satureja hortensis L. The pharmaceutical form comprises the dry extract of abovementioned mix or the mix of dry extracts of the plants and pharmaceutically acceptable additives. The mentioned mix and pharmaceutical forms are used for treatment of bronchitis, pneumonia, pleurisy and tuberculosis. The technical effect is achieved by the following properties of the plants cmprised in the mix:

Marsh-mallow roots (Althaea) contain abundance of mucus, starch, pectins, phytosterol and mineral salt. They have coating, softening, expectorative properties and reduce inflammatory process, especially on mucous tunics, accelerate absorption of the remedy, which helps longer and complete local action.

Elecampane roots (Inula helenium L) contain essential oil (mixture of quiterpene lactones) vitamins, saponin, mucus, pigments, alkaloid and polysaccharide (inulin). It is used for reducing the secretion of bronchus and antiseptic, antibacterial expectorative for diluting thick consistence.

Coltsfoot leaves (Tussilago farfara L) is rich in poly saccharide (mucus), saponin, bitter glycoside, carotenoid, tanning agent, organic acid and flavonoid. Coltsfoot leaves have coating properties on oral cavity, throat and on mucous tunics of esophagus, in this way it protects from the external irritation, besides mucus and saponin liquife dry secretion in respiratory tracts and facilitate their fast evacuation. Coltsfoot leaves have expectorative and anti-inflammatory action.

Pine buds (Pinus sylvestris L.) contain resinous and tanning agents, essential oil, vitamins. Galenical of pine buds strengthens the secretion activity of respiratory tracts mucous tunics. They also have expectorative, antiseptic and anti-inflammatory action, have bacteriostatic action on microflora of pharyngonasal and oral cavities.

Sage herb (Salvia officinalis L.) contains plavonoids, alkaloids, essential oil, tanning agent, vitamins, iridine. It has anti-inflammatory and moderate bacteriostatic action, especially towards gram-positive microflora.

Chamomile flower (Matricaria chamomilla L.) contains essential oil (chamazulene, matricine, macricarine,) plavonoids, coumarin, carotinoid, vitamin C, organic acid and polysaccharide. Chamomile flower has spasmolytic, anti-inflammatory, antiseptic, sedative action.

Garden Peppermint herb leaves (Mentha piperita L) contain essential oil in large quantities, its main component is menthol. Besides, it consists of plavonoids, organic acid and tanning agents. Mint galena preparations have sedative, spasmolytic, cholagogic, antiseptic and analgetic action.

Motherwort (Leonurus quinquelobatus Gilib) contains alkaloids, essential oil, plavonoids, vitamins, tanning agents, bitter glycosides. Motherwort has full-blown sedative action.

Pot marigold (Calendula officinalis L.) contains carotinoid, (rebinsactine, lycopine, violocsadine) resin material, triterpenic glycosides, mucus and bitter glycosides, organic acids, plavonoids. Its main pharmacological properties are: anti-inflammatory, wound incarnation, bacteriostatic, spasmolytic and cholagogic.

Savory herb (Satureja hortensis L.) or Thymus vulgaris contains essential oil, its main compound components are thymol and carvacrol, also tanning agents, macro and micro elements and etc. They have expectorative, bactericidal anti-spasm and anti-inflammatory action and it affects gram-negative mircoflora and fungi as well as antibiotic resistant microflora.

One aspect of the present invention is herbal mix, that comprises marsh-mallow roots, elecampane roots, coltsfoot leaves, pine buds, sage herb, chamomile flower, peppermint, motherwort, pot marigold flowers, savory herb.

In the preferred embodiment of the present invention the herbal mix comprises components in the following ratio, mass %:

Marsh -mallow roots 2-15

Elecampane roots 2-15 Coltsfoot leaves 2-15

Pine buds 2-15

Sage herb 2-15

Chamomile flower 2-15

Peppermint herb 2-15 Motherwort 2-15

Pot marigold flowers 2-15

Savory herb 2-15

In the still more preferred embodiment of the present invention the herbal mix the herbal mix comprises components in the following ratio, mass %: Marsh -mallow roots 10

Elecampane roots 10

Coltsfoot leaves 10

Pine buds 10

Sage herb 10 Chamomile flower 10

Peppermint herb 10

Motherwort 10

Pot marigold flowers 10

Savory herb 10

The herbal mix is prepared in the following way: the herbal raw material is dried, grinded into small pecieces and then mixed.

Example 1. The mix comprises the components in the following ratio, mass %: Marsh -mallow roots 10

Elecampane roots 10

Coltsfoot leaves 5

Pine buds 15

Sage herb 15 Chamomile flower 15

Peppermint herb 5

Motherwort 10

Pot marigold flowers 10

Savory herb 5

Example 2. The mix comprises the components in the following ratio, mass %:

Marsh -mallow roots 15

Elecampane roots 10

Coltsfoot leaves 15 Pine buds 10

Sage herb 5

Chamomile flower 10

Peppermint herb 5

Motherwort 10 Pot marigold flowers 15

Savory herb 5 Example 3. The mix comprises the components in the following ratio, mass %:

Marsh -mallow roots 10

Elecampane roots 5 Coltsfoot leaves 10

Pine buds 15

Sage herb 5

Chamomile flower 15

Peppermint herb 5 Motherwort 10

Pot marigold flowers 15

Savory herb 10

The therapeutic indications of the herbal mix are: bronchitis, pneumonia, pleurisy, tuberculosis. For the purpose of treatment, aqueous extract of plant species is prepared. The plant species are placed into the boiling water in the volumetric amount 1 : 10. The obtained mix is boiled during 15 min. stayed 45 min to get cooler, then bolted, after that it is ready for use.

For the purpose of treatment with the mentioned therapeutic agent patient drinks 120 ml. of decoction heated at average temperature three times a day (minimal dose), 150 ml. four times a day

(maximum dose). It is better to start treatment in minimal doses, because by case monitoring, anamnesis and corresponding researches doctor could choose the treatment dose.

One more aspect of the invention is the pharmaceutical form, which contains the dry extract of plant species presented by the active ingredients or the dry extract mix of the mentioned species constituent plants and pharmaceutically acceptable additives. The pharmaceutical form can be tablet, capsule and syrup type.

In case, if pharmaceutical form has tablet or capsule form, in the primary variant of the invention realization pharmaceutical forms contain components in the following correlation, mass portions:

Active ingredients 200.0-400.0 Additives 140-260

In case of using dry extract received from the plants in type of active ingredients, in the primary variant of the invention realization pharmaceutical forms contain components in the following correlation, mass portions:

Extract of Marsh -mallow roots 20.0-40.0 Extract of Elecampane roots 20.0-40.0

Extract of Coltsfoot leaves 20.0-40.0

Extract of Pine buds 20.0-40.0

Extract of Sage herb 20.0-40.0

Extract of Chamomile flower 20.0-40.0 Extract of Peppermint herb 20.0-40.0

Extract of Motherwort 20.0-40.0

Extract of Pot marigold flowers 20.0-40.0

Extract of Savory herb 20.0-40.0

Additive 140-260 For preparation of pharmaceutical forms of tablet type for additive can be used any additive known in pharmaceutical production. In the primary variant of the invention realization magnesium carbonate, starch, polyvinylpyrrolidone, calcium stearate, talc are used, which content in the primary variant of the invention realization is, mass portions:

Magnesium carbonate 20.0-40.0 Starch 30.0-70.0

Polyvinylpyrrolidone 80.0-120.0

Calcium stearate 5.5-12.5

Talc 6.0-14.0

For preparation of pharmaceutical forms of capsule type for additive can be used any additive known in pharmaceutical production. In the primary variant of the invention realization lactose and calcium stearate are used, which content in one capsule is, mass portions: Lactose 160.0-220.0 Calcium stearate 4.5-14.5

The treatment form can also be produced in syrup type, this treatment form in the primary variant of the invention realization comprises components in the following correlation, mass portions: Active ingredients 1.0-6.0

Additive 4.5-14.5 In case of using the dry extract of species in active ingredients type in the primary variant of the invention realization the mentioned pharmaceutical form comprises the components in the following correlation, mass portions:

The dry extract of species 1.0-6.0

Additive 85-150 In case of using the dry extract of species received from the plants in active ingredients type, in the primary variant of the invention realization the mentioned pharmaceutical form comprises the components in the following correlation, mass portions: Extract of Marsh -mal low roots 0.1-6

Extract of Elecampane roots 0.1-6 Extract of Coltsfoot leaves 0.1-6

Extract of Pine buds 0.1-6

Extract of Sage herb 0.1-6

Extract of Chamomile flower 0.1-6

Extract of Peppermint herb 0.1-6 Extract of Motherwort 0.1-6

Extract of Pot marigold flowers 0.1-6

Extract of Savory herb 0.1 -6

Additives 85-150

For producing the pharmaceutical form in syrup type for additive can be used any additive known in pharmaceutical production. In the primary variant of the invention realization as additive can be used fructose, sorbite and water in the following correlation, mass portions: Fructose 0.2-0.4

Sorbite 5.-20.0

Water 80-120

For receiving the mentioned pharmaceutical forms the dry extract is received by any known technology, that in one of the variants provides for the following stages: preparation of the plant species, its several extraction by water, connection of received grind and strain, to thick the filtrate and to dry at the end before receiving the dry extract (powder). In case, if of pharmaceutical form is received in active ingredients type by using the dry extract mix received from the plant, in technological process would be foreseen, accordingly, grinding of separately taken plants and their multiple extraction by water, after which it will be continued unchangeable.

As a result of the experiment the optimal conditions of the plants raw material extraction was generate: the degree of plants raw material grinding 2.5 mm. raw material - extragenic (water) correlation 1 :5, extraction temperature rate not more than 90-95 ⁰ C, double extraction each duration is 1.5 h. The grinds are strained in vacuum-filter, thickening is done in vacuum- evaporating device, reactionary weight at 40-50 ⁰ C before receiving 1/10 of part the initial volume, the concentrated extract is dried in sprayer drier.

After receiving the dry extract double extraction of the plants raw material provide the maximal passing of the all biologically active material from the raw material by hot water.

By the dry extract and photochemical analysis of the presented phytopreparations was stated the presence of such biologically active material as: polysaccharides, essential oil, saponins, plavonoids, tanning agents and organic acids. The mentioned substances have coating, anti- inflammatory, mucous tunics of respiratory tracts and alleviation of its evacuation. Taking into consideration the hydroscopic, friable, bulk strength of the dry extract the tableting technology was accomplished, which includes the following technological stages: mixing of dry plants raw material with starch and magnum carbonate, received mix wetting with polyvinylpyrrolidone, producing of the wet granulation, drying of the granules, producing of the dry granulation, adding cose and talc to the granules and tableting on the tablet machine. The main example of tableting accomplishment provides for the following stages: 30.0 kg. dry extract is placed in the stirrable container, add 5.0 kg. starch and 3.0 kg. magnum carbonate and are shifting during 20 min. Then add 10.0 kg. polyvinylpyrrolidone, are shifting during 30 min. and produce wet granulation on the vertical type granulator. The received granules are dried on the shelves in the exsiccator using the air circulation. The dried granules are passed through the granulator strainer with the hole of 1.5 mm. 110.0 g. Talc and 90.0 calcium stearate are added to the dried granules and are tableted on the automatic tableting machine on 7kN pressure. The dissolubility of received tablets is 20 min. and - solubility 80%. that meets the state pharmacopeia conditions. Due to the state pharmacopeia the monitoring was carried out for tablets received in the optimal conditions (The State Pharmacopeia, v. II, Tbilisi, 2003, pp. 84-92):

Determination of the average weight by weighing 20 tablets to within 0.000 Ig. and compounds

O.5±5% g.

Dissolubility was determined on the "rocking basket". Dissolubility is 20 min. Solubility was determined on the "spinning basket" equipment. During the 45 min. solute quantity is 85%.

Mechanical firmness was examined on compression using "Evreka" firm TBT model equipment and compounds 0.78

Mechanical firmness on wearing out was determined using 545-Ak- 1 type friabilator and compounds 98%. Stability of tablets was determined using obsolescence shortcut method under 60 ⁰ C temperature conditions and compounds 2 years.

The tableted treatment agent has several advantages. At first, taking is convenient in all concrete conditions, any part of the day and in any place (home, traveling and etc.) secondly, tablets have convenient medication form for keeping and transportation, because, it is packed on the polymeric blister or plastic vial.

Tableted treatment form is packed on the polymeric blister or plastic vial.

The capsule production in the possible variant presented in the application includes the following stages: lactose and magnesium stearate are mixed with dry extract, the received mix is assorted using capsule filling automatic laboratory or factory equipments. The weight of capsule input is 0.5 g.

In rating of capsule quality the following parameters are defined: average weight, dissolubility and solubility.

The average weight of received capsules are 0.5 g. dissolubility is 20 min, solubility is 80%, that meets the state pharmacopeia conditions. (The State Pharmacopeia, v. II, Tbilisi, 2003, pp. 69-71). The preparation of the therapeutic agent of syrup type in pharmaceutical practice is achieved by generally accepted technology.

In ration of syrup quality the following parameters are defined: nominal volume firmness and refraction.

The nominal volume of the received syrup is 100 ml. firmness 1.108, refraction - 1,357.

Example 1.

Tablet contains the component in the following correlation, mass portions: Species dry extract 300

Potassium carbonate 21 Starch 53

Polyvinylpyrrolidone 100

Magnesium stearate 12,5

Talc 13,5

Example 2.

The capsule contains the components in the following correlation, mass fraction:

Extract of Marsh -mallow roots 40

Extract of Elecampane roots 40

Extract of Coltsfoot leaves 30 Extract of Pine buds 30

Extract of Sage herb 30

Extract of Chamomile flower 30

Extract of Peppermint herb 30

Extract of Motherwort 30 Extract of Pot marigold flowers 20

Extract of Savory herb 20

Lactose 186

Magnesium stearate 14

Example 3.

The syrup contains the components in the following correlation, mass portions:

Extract of Marsh -mallow roots 0.5

Extract of Elecampane roots 0.5

Extract of Coltsfoot leaves 0.5 Extract of Pine buds 0.5

Extract of Sage herb 0.5

Extract of Chamomile flower 0.5

Extract of Peppermint herb 0.5

Extract of Motherwort 0.5 Extract of Pot marigold flowers 0.5

Extract of Savory herb 0.5

Fructose 0.3

Sorbite 15

Water 100 The therapeutic index of treatment forms are: bronchitis, pneumonia, pleurisy,

tuberculosis.

For the purpose of treatment the single therapeutic dosage of the active substance dry extract is 300 mg. (0.3 g.), but the daily dosage is 900 mg. (0.9g.)

The methodology of the presented therapeutic agent is the following. During the day it is possible to take it 3 or 4 times. The treatment duration of the diseases, mentioned in the application, is variable and continues to the final ending of the treatment according the doctor's recommendations. Due to the character and severity of the respiratory tract diseases duration of the tablets prescription is different, a) are left in the oral cavity before the absolute aspiration, b) one tablet is dissolved 100 ml (half cup) hot water and is drunk all; c) take perorally with water in the small quantities. Capsuls are taken perorally three times a day with water in the small quantities.

Besides, during the treatment with the presented therapeutic agent at the acute condition of the disease, the patient can be treated by symptomat treatment using the classical medicine.

After finishing the main course of treatment, like all chronic disease, it is possible to take preventive treatment once or twice a year.

Examples of treatment.

Example 1. Patient aged 46, male, diagnosis - fibrous - cavernous tuberculosis of both lungs, acute phase, complaints - aching pain in shoulder area, weakness, quickened respiration, protracted cough, bleeding, lack of appetite, increased ESR in the blood analysis, BK+ in phlegm. For years the patient had been taking drug treatment with temporary effect.

The patient was treated with the decoction of the abovementioned herbal species, he took 120 ml. warmed decoction three times a day after 15 min. from the meal during six month.

The status of patient improved, pain eliminated, respiration regulated, work-status increased. Three years past since patients treatment and the patient doesn't have any complaints.

Example 2. Patient aged 27, male, diagnosis - focal sown tuberculosis of the right lung, left-sided exudative pleurisy. Numerous polymorphic stains revealed on the right side. The patient suffered from high temperature, cough, weakness, lack of appetite, loss of weight, pale skin. The patient with increased ESR underwent the classical medical treatment for 2 years with positive results of short duration.

The patient was treated by the proposed tablet. He was given three tablets a day after 15 min. from the meal. The duration of the treatment was six months.

The temperature is regulated, cough reduced, gained weight, work-status increased. Two years passed since the patient's treatment and he doesn't have any complaints during this period.

Example 3. Patient aged 36, female, diagnosis - chronic bronchitis. In anmnesis revealed the disturbing cough with vision of mucus, during exercise stress easily getting tired, dyspnea, often respiratory infections. The patient was treated by the proposed syrup. She took a table-spoon of syrup four times a day 15 min. after the meal. The treatment duration was three months.

Cough and dyspnea were eliminated, increased body's reaction against infection.

Example 4. Patient aged 31, female, diagnosis - lymphadenopathy of mediastinum, plural caverns in the lower lobes of the both lungs, areas of infiltration in the parenchyma and right-sided, exudate pleurisy. Conglomerate of size 1,3X2,4 cm. and also a lymphatic gland with the diameter of 1,5 cm. were found in the mediastinum. A cavity with unclear contours and uneven walls size 4,0X2,6 is visible near the lung hilum. In the lumens of the cavity is a stain of issue density. The patient suffered from the high temperature and anxiety cough with bloody phlegm. The patient is treated for a year with the proposed capsule. Was given one capsule four times a day 15 min. after the meal.

The temperature is regulated, areas of infiltration cleared away, lymphatic glands reduced in size, bronchus became permeable, pleurisy isn't revealed, work-status returned. Recovery dynamic is raucously satisfactory.

Example 5. Patient aged 12, male, diagnosis - chronic bronchial pneumonia, had weakness, periodical cough with mucopurulent sputum, right low part could be heard by auscultation.

The patient was treated for two weeks with the above proposed plant species decoction 120 ml. warmed three times a day 15 min. after the meal. The patient doesn't cough, the vesical respiration became active and is possible to hear by auscultation.

Besides the therapy indexes for increasing the reactivity of the body, it is purposeful to take herbal treatment agents.

The presented phyto preparation doesn't consist stiff, synthetic and toxic ingredients. It is safe, effective, convenient in use, has wide pharmacologic properties - anti- inflammatory, coating, expectorative, antitussive, spasmogenic, antiseptic, that gives possibility to treat not only the mail diseases, but also its pathologies. The presented phyto preparation is used as for dry cough, as for productive cough (with much mucus) and its pathologies as well. For including nontoxic components the therapeutic agent can be taken by children and adults as well, also by the aged too. The efficiency of the abovementioned therapeutic agent is determined by the strengthening of body

immunity. The invention enlarges the choice of treatment agents prepared by herbal raw material and increases efficiency of the treatment.